Stem Cell Information Management System

Abstract

This invention provides a stem cell information management system for centrally managing information in the following processes: accepting a manufacturing commission for stem cells made from somatic cells; transporting somatic cells collected from a somatic cell provider or stem cells made from said somatic cells; inspecting said somatic cells or said stem cells; manufacturing process for making said stem cells from said somatic cells; and storing said stem cells. The stem cell information management system includes: a storage unit for storing: collection schedule, inspection schedule, manufacturing schedule, and storage schedule; and a determination unit for determining, based on the stored collection schedule, inspection schedule, manufacturing schedule, storage schedule, and storage schedule, at least the collection date for collecting said somatic cells from said somatic cell provider.

Description

[0001] This application is a divisional application of the original Chinese patent application filed on August 3, 2017, with application number 201710656614.9, entitled "Stem Cell Manufacturing System, Information Management System, Delivery and Cryopreservation Equipment". Technical Field

[0002] This invention relates to the manufacturing technology of pluripotent stem cells, and more particularly to stem cell manufacturing systems, stem cell information management systems, cell delivery equipment, and stem cell cryopreservation equipment. Background Technology

[0003] Embryonic stem cells (ES cells) are stem cells constructed from early human and mouse embryos, possessing pluripotency and the ability to differentiate into all types of cells found in living organisms. Human ES cells are considered suitable for cell transplantation to treat various diseases, including Parkinson's disease, juvenile diabetes, and leukemia. However, like organ transplantation, ES cell transplantation faces the risk of rejection. Furthermore, the use of ES cells created by destroying human embryos faces significant ethical opposition.

[0004] In this regard, Professor Shinya Yamanaka of Kyoto University successfully constructed induced pluripotent stem cells (iPS cells) by introducing four genes—Oct3 / 4, Klf4, c-Myc, and Sox2—into somatic cells, for which he was awarded the 2012 Nobel Prize in Physiology or Medicine (see, for example, Japanese Patent No. 4183742). iPS cells are ideal pluripotent cells that do not present rejection reactions or ethical issues, and their use in cell transplantation is anticipated. Summary of the Invention

[0005] Induced stem cells, such as iPS cells, are constructed, cultured, and cryopreserved by introducing inducing factors such as genes into cells. However, for example, there are problems with the production and industrialization of clinical-grade iPS cells (GLP, GMP grade).

[0006] 1) Cost

[0007] Clinical iPS cells need to be fabricated and stored in a highly clean environment. However, maintaining such cleanrooms is extremely costly. Therefore, optimizing cleanroom usage to reduce costs is a key challenge for industrialization.

[0008] 2) Quality

[0009] The entire process from stem cell creation to preservation is complex and often requires manual intervention. Furthermore, stem cell production tends to rely on individual skill levels. Therefore, the quality of iPS cells can vary depending on the producer and the date of production. Additionally, the quality of iPS cells depends on the quality of the somatic cells used as raw materials. Therefore, managing the delivery time and temperature until the somatic cells are received, as well as the characteristics of the somatic cell provider (gender, age, medical history, genetic background, etc.), and integrating this diverse information becomes crucial.

[0010] 3) Time

[0011] To prevent cross-contamination of somatic cells and iPS cells with other individuals in a cleanroom, only one dose of iPS cells can be prepared at a time in the cleanroom. Furthermore, the construction and quality evaluation of iPS cells take a considerable amount of time. However, if iPS cells for multiple recipients were prepared individually in a single room, the time required for preparation would be extremely long. Therefore, a system capable of simultaneously producing iPS cells for multiple recipients is needed. Additionally, since cultured cells are living organisms, they will die if not delivered, processed, and preserved at the appropriate time. Especially during simultaneous production, without centralized management of the entire process from somatic cell collection to iPS cell construction and preservation, it is impossible to provide iPS cells to multiple recipients in a timely manner.

[0012] 4) Pollution

[0013] The primary source of contamination in a cleanroom is people, so they must be eliminated first. Furthermore, even if iPS cells from multiple recipients can be produced simultaneously and in large quantities, contamination cannot be prevented unless the entire process from somatic cell collection to stem cell construction and preservation is constructed as a closed system. Moreover, when simultaneous manufacturing is the goal, the risk of sample mixing and cross-contamination is high.

[0014] 5) Human Resources

[0015] As mentioned above, currently, iPS cell production is mostly done manually, but there are few technicians capable of producing clinically usable iPS cells. There are a series of complex operational issues from stem cell construction to preservation. Clinical cell culture requires three steps: confirming the Standard Operating Procedure (SOP), following the SOP, and confirming whether the SOP has been followed. Performing these steps manually is highly inefficient. This can lead to human errors such as confusion of somatic cells among multiple users, confusion of culture reagents or necessary materials, and procedural errors. Furthermore, cell culture requires 24-hour daily management, and stem cells can be preserved for decades; therefore, relying solely on manual management has limitations.

[0016] Therefore, there is a desire for a technology that can produce and preserve stem cells in a timely manner with low cost and high quality management, while preventing contamination.

[0017] One aspect of this disclosure provides a stem cell manufacturing system for producing stem cells from somatic cells, comprising: one or more closed manufacturing devices for producing stem cells from somatic cells; one or more drive devices connected to the manufacturing devices and driven in a manner that maintains the manufacturing devices in an environment suitable for stem cell production; one or more storage devices for cryopreserving the produced stem cells; a first storage device for storing whether somatic cells are introduced into the manufacturing devices as a first state; a second storage device for storing whether the manufacturing devices are connected to the drive devices as a second state; and a third storage device for storing whether the produced stem cells can be placed in the storage device as a third state.

[0018] A further embodiment of this disclosure provides a stem cell information management system for centralized management of information in: an acceptance process for accepting a manufacturing commission for stem cells made from somatic cells; a delivery process for delivering somatic cells collected from a somatic cell provider or stem cells made from somatic cells; an inspection process for examining somatic cells or stem cells; a manufacturing process for making stem cells from somatic cells; and a storage process for storing stem cells. The aforementioned stem cell information management system comprises: a storage unit storing: a collection schedule for collecting somatic cells from a somatic cell provider; an inspection schedule for examining somatic cells; a manufacturing schedule for one or more manufacturing devices for making stem cells from somatic cells; a storage schedule for one or more storage devices for cryopreserving the manufactured stem cells; and a storage schedule for the storage location of the aforementioned storage devices; and a determination unit that, based on the stored collection schedule, inspection schedule, manufacturing schedule, storage schedule, and storage schedule, determines at least the collection date for collecting somatic cells from a somatic cell provider.

[0019] This disclosure also provides a cell delivery device for delivering somatic cells to one or more closed-loop fabrication devices for producing stem cells from somatic cells collected from a somatic cell provider, or for delivering stem cells to a stem cell storage location. The device comprises: a somatic cell collection vial or a stem cell freezing vial; the somatic cell collection vial contains the collected somatic cells and is equipped with a first somatic identification device including provider identification information for identifying the somatic cell provider and fabrication device identification information for identifying the fabrication device; the stem cell freezing vial contains stem cells frozen after fabrication by the fabrication device and is equipped with provider identification information. The device comprises: a second entity identification device for identifying the storage location of the stem cells, including identification information of the production device and identification information of the storage location; a delivery container configured to hold one or more somatic cell collection vials or one or more stem cell freezing vials; a reading device configured to read at least one of the provider identification information, production device identification information and storage location identification information contained in the first or second entity identification device; and a delivery vehicle for delivering the delivery container containing the somatic cell collection vials or stem cell freezing vials based on the read production device identification information or storage location identification information.

[0020] A further embodiment of this disclosure provides a stem cell cryopreservation device for cryopreserving stem cells made from somatic cells collected from a somatic cell provider. The device comprises: stem cell cryopreservation vials discharged from one or more sealed production devices and containing frozen stem cells; one or more preservation devices for cryopreserving the stem cell cryopreservation vials; a storage container for housing the preservation devices; and a first conveying device for moving the preservation devices into or out of the storage container. The preservation device includes: a receiving section for housing one or more stem cell cryopreservation vials and a freezing tank for housing a cold-insulating medium for freezing the stem cell cryopreservation vials.

[0021] Another aspect of this disclosure is a stem cell information management system, which is a stem cell information management system equipped with a terminal device for accepting stem cell manufacturing orders and a server device. The server device manages the somatic cell acceptance process, the stem cell manufacturing process, the storage process of the manufactured stem cells, and the delivery process of the manufactured stem cells. The terminal device has: a receiving unit that accepts manufacturing orders containing the expected collection date of somatic cells and receives provider identification information for identifying the somatic cell provider; and a terminal sending unit that sends the accepted manufacturing orders and provider identification information to the server device. The server device has: a storage unit that stores the available collection date of somatic cells, the available time period for stem cell manufacturing, and the available storage location and storage period for the manufactured stem cells; a receiving unit that receives the sent manufacturing orders and provider identification information; and a determining unit that determines the information based on the expected collection date contained in the received manufacturing order and the stored available collection date. The process involves several steps: first, determining the somatic cell collection date; second, determining the stem cell production period based on the determined somatic cell collection date and the stored production period; third, determining the somatic cell acceptance date based on the determined somatic cell collection date and the stored production period; fourth, determining the storage location and storage period of the produced stem cells based on the determined production period and the stored storage location and storage period; and fifth, determining the stem cell shipment date based on the determined production period and the stored storage location and storage period. The storage processing unit stores the determined somatic cell collection date, production period, somatic cell acceptance date, storage location and storage period, and stem cell shipment date in a storage unit, associated with the received provider identification information. Finally, the server sending unit sends the somatic cell collection date, production period, somatic cell acceptance date, storage location and storage period, and stem cell shipment date, which are stored in association with the provider identification information, to the somatic cell provider indicated by the stored provider identification information.

[0022] A further embodiment of this disclosure provides a stem cell information management system comprising: an order management terminal for accepting stem cell manufacturing orders; an acceptance management terminal for managing the acceptance of somatic cells used to manufacture stem cells; a manufacturing process management terminal for managing the stem cell manufacturing process; and a storage management terminal for managing the storage of the manufactured stem cells. The order management terminal includes: a first storage unit; an acceptance unit that accepts manufacturing orders containing the desired collection date of the somatic cells and accepts provider identification information for identifying the somatic cell provider; and a first determination unit that determines the collection date of the somatic cells based on the desired collection date contained in the accepted manufacturing order. The terminal includes: a first output unit that outputs the determined somatic cell collection date to a first medium, and a first storage processing unit that associates the determined somatic cell collection date with the identification information of the receiving provider in a first storage unit; a receiving management terminal that includes: a second storage unit that stores the collection date of collectable somatic cells, a second output unit that outputs the stored collection date to a second medium, a second determining unit that determines the receiving date of somatic cells based on the somatic cell collection date conveyed by the first medium, and a second storage processing unit that stores the determined receiving date of somatic cells in the second storage unit; and a manufacturing process management terminal that includes: a manufacturing time for the production of stem cells. The third storage unit stores the stem cells in a third storage section; the third determining unit determines the stem cell production period based on the somatic cell collection date and the stored production period as communicated by the first medium; the third output unit outputs the stored stem cell production period to the third medium and the determined stem cell production period to the fourth medium; and the third storage processing unit stores the determined stem cell production period and the stem cell production period in the third storage section. The storage management terminal includes a fourth storage unit that stores the storage location and storage period of the produced stem cells. The storage unit outputs the stored storage location and storage period to the fifth medium via a fourth output unit, and a fourth determining unit determines the storage location and storage period of the produced stem cells based on the stem cell production period communicated by the fourth medium and the stored storage location and storage period; the first determining unit determines the somatic cell collection date based on the expected collection date and the collection date communicated by the second medium; the second determining unit determines the somatic cell acceptance date based on the somatic cell collection date and the production period communicated by the third medium; and the third determining unit determines the stem cell shipment date based on the stem cell production period and the storage location and storage period communicated by the fifth medium. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of a stem cell manufacturing system according to one embodiment.

[0024] Figure 2A side view of a somatic cell collection vial, a stem cell freezing vial, a culture reagent vial, and a material vial for stem cell production according to one embodiment.

[0025] Figure 3A This is a cross-sectional view of a manufacturing apparatus according to one embodiment. Figure 3B This is a cross-sectional view of the drive unit. Figure 3C A cross-sectional view of the fabrication device connected to the drive unit.

[0026] Figure 4 This is an enlarged cross-sectional view of a drive device according to one embodiment.

[0027] Figure 5 This is a perspective view of a storage device according to one embodiment.

[0028] Figure 6 This is a block diagram of a stem cell manufacturing system according to one embodiment.

[0029] Figure 7 This is a functional block diagram of a stem cell manufacturing system that incorporates a field system in one implementation.

[0030] Figure 8 This is a flowchart illustrating the operation of a stem cell manufacturing system according to one embodiment, based on the transition from a first state to a third state.

[0031] Figure 9 This is a flowchart illustrating the operation of a stem cell manufacturing system based on a fourth state according to one embodiment.

[0032] Figure 10 This is a flowchart illustrating the operation of a stem cell manufacturing system based on a fourth state according to one embodiment.

[0033] Figure 11 This is a flowchart illustrating the operation of a stem cell manufacturing system based on a sixth state according to one embodiment.

[0034] Figure 12 This is a flowchart illustrating the operation of a stem cell manufacturing system according to a seventh state in one embodiment.

[0035] Figure 13 This is a flowchart illustrating the operation of a stem cell manufacturing system according to an eighth state in one embodiment.

[0036] Figure 14 This is a schematic diagram illustrating the server-type configuration of a stem cell information management system according to one embodiment.

[0037] Figure 15This is a block diagram illustrating the server-type configuration of a stem cell information management system according to one embodiment.

[0038] Figure 16 This is a block diagram illustrating the media utilization configuration of a stem cell information management system according to another embodiment.

[0039] Figure 17 This is a sequence diagram illustrating the server-type operation of a stem cell information management system according to one embodiment.

[0040] Figure 18 This is a sequence diagram illustrating the media-utilization operation of a stem cell information management system according to another embodiment.

[0041] Figure 19 This is a diagram illustrating the provider scheduling table, collection agency scheduling table, and inspection agency scheduling table of a stem cell information management system according to one embodiment.

[0042] Figure 20 This diagram illustrates a manufacturing location schedule, a fabrication device schedule, and a preservation device schedule for a stem cell information management system according to one embodiment.

[0043] Figure 21 This is a diagram illustrating the order form and acceptance form of a stem cell information management system according to one embodiment.

[0044] Figure 22 This is a diagram illustrating the creation table, storage table, storage location scheduling table, and storage table of a stem cell information management system according to one embodiment.

[0045] Figure 23 This is a block diagram of a somatic cell delivery container according to one embodiment.

[0046] Figure 24 This is a functional block diagram of a heating and cooling device in a somatic cell delivery container according to one embodiment.

[0047] Figure 25 This is a functional block diagram of a somatic cell coagulation monitoring device in a somatic cell delivery container according to one embodiment.

[0048] Figure 26 This is a diagram illustrating the transport table of a stem cell information management system according to one embodiment.

[0049] Figure 27 This is a flowchart illustrating the operation of a stem cell information management system during delivery according to one embodiment.

[0050] Figure 28 This is a block diagram of a first inspection device according to one embodiment.

[0051] Figure 29 This is a functional block diagram of a first inspection device according to one embodiment.

[0052] Figure 30 This is a flowchart illustrating the operation during an inspection of a stem cell information management system according to one embodiment.

[0053] Figure 31 This is a flowchart illustrating the operations involved in creating a stem cell information management system according to one embodiment.

[0054] Figure 32 This is a flowchart illustrating the operations involved in creating a stem cell information management system according to one embodiment.

[0055] Figure 33 This is a flowchart illustrating the operations involved in creating a stem cell information management system according to one embodiment.

[0056] Figure 34 This is a block diagram of a second inspection device and a third inspection device according to one embodiment.

[0057] Figure 35 This is a functional block diagram of a second inspection device according to one embodiment.

[0058] Figure 36 This is a functional block diagram of a third inspection device according to one embodiment.

[0059] Figure 37 This is a flowchart illustrating the operation during an inspection of a stem cell information management system according to one embodiment.

[0060] Figure 38 This is a functional block diagram of a site system applied in a stem cell information management system according to one implementation method.

[0061] Figure 39 This is a perspective view of a somatic cell delivery container in a cell delivery device according to one embodiment.

[0062] Figure 40 This is a perspective view of a stem cell delivery container in a cell delivery device according to one embodiment.

[0063] Figure 41 This is a block diagram of a stem cell delivery container according to one embodiment.

[0064] Figure 42 This is a flowchart illustrating the operation of a cell delivery device according to one embodiment.

[0065] Figure 43 This is a functional block diagram of a site system used in a cell delivery device according to one embodiment.

[0066] Figure 44 This is a schematic diagram of a stem cell cryopreservation device according to one embodiment.

[0067] Figure 45 This is a block diagram of a stem cell cryopreservation device according to one embodiment.

[0068] Figure 46 This is a functional block diagram of a site system used in a stem cell cryopreservation device according to one embodiment. Detailed Implementation

[0069] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the drawings, the same or similar constituent elements are given the same or similar reference numerals. Furthermore, the embodiments described below do not limit the technical scope of the invention as stated in the claims or the meaning of the terminology.

[0070] 1. Stem cell manufacturing system

[0071] Figures 1 to 6 This diagram illustrates the configuration of the stem cell manufacturing system 100 in this embodiment. (See diagram below.) Figure 1 As shown, the stem cell manufacturing system 100 includes one or more closed-loop manufacturing devices 101 for producing stem cells from somatic cells, capable of simultaneously producing stem cells from multiple recipients. The closed-loop manufacturing device 101 inserts a vial 102 containing a sealed container of somatic cells, automatically produces stem cells, and discharges the vial 103 containing the frozen stem cells. The discharged vial 103 is then transferred to one or more storage devices 120 for cryopreservation. In this embodiment, a system for producing iPS cells from blood cells has been described; however, it should be understood that systems for producing iPS cells from cells derived from skin, systems for producing somatic stem cells from other somatic cells, and systems for producing stem cells from animal cells are also applicable.

[0072] like Figure 1As shown, the stem cell manufacturing system 100 includes a drive unit 130 that operates to maintain the closed manufacturing apparatus 101 in an environment suitable for stem cell production. Furthermore, the stem cell manufacturing system 100 includes: a transport unit 140 for transporting at least one of the various vials 102-105 stored in the storage device 150 to the manufacturing apparatus 101; a transport unit 141 for transporting the manufacturing apparatus 101 to the drive unit 130 or vice versa; and a transport unit 142 for transporting the stem cell frozen vials 103 discharged from the manufacturing apparatus 101 to the storage device 120. These transport units 140-142 are automated devices that operate autonomously according to a teaching procedure; in other embodiments, these transport units 140-142 may also be belt conveyor systems. In another embodiment, two or three of the transport units 140-142 are a single unit.

[0073] Reference Figure 1 The stem cell manufacturing system 100 includes a control device 160 that is wired or wirelessly connected to the drive unit 130, the transport units 140-142, and the storage unit 120, and controls the drive unit 130, the transport units 140-142, and the storage unit 120. Furthermore, the control device 160 is wired or wirelessly connected to a host computer 170 located in the cloud, and accesses various information obtained from acceptance, transport, inspection, and storage processes other than the manufacturing process. The host computer 170 includes an acceptance storage device (see reference) that stores at least the provider information of somatic cells when accepting a stem cell manufacturing order. Figure 15 (symbol 202). Furthermore, the host computer 170 sends various information, such as abnormal warnings, to a portable terminal 180 located at a remote distance. Examples of portable terminals 180 include, for instance, smartphones used by somatic cell donors.

[0074] like Figure 2 As shown, the vials include: a somatic cell collection vial 102 containing collected somatic cells, a stem cell freezing vial 103 containing frozen stem cells, a culture reagent vial 104 containing culture reagents, and a stem cell production material vial 105 containing materials other than culture reagents used in stem cell production. For ease of understanding, Figure 2 Only four types of vials 102-104 are shown in the illustration, but in reality, there are many different types of vials. These vials 102-104 are equipped with an individual identification device 106 for identifying individuals. The individual identification device 106 can be a semiconductor chip utilizing RFID, a one-dimensional barcode, a QR code (registered trademark), an SP code, or other similar two-dimensional code.

[0075] Figure 2The individual identification device 106 shown contains at least a provider ID for a designated somatic cell provider. Figure 1 The conveying devices 140-142, the drive device 130, and the storage device 120 shown in the figure are equipped with a reading device 107 for reading information from the individual identification device 106 (see reference). Figure 2 Based on the provider ID read from the vial, provider information can be read from the host computer 170. This provider information may include the somatic cell provider's informed consent form, nationality, address, gender, age, blood type, past medical records, medication prescription records, health diagnosis results, and information about family members who have previously produced stem cells. In other embodiments, the individual identification device 106 may contain this provider information, in which case the provider information may be encrypted.

[0076] Figure 2 The individual identification device 106 shown includes, in addition to a provider ID, at least one of the following: an order ID for identifying the acceptance of a stem cell manufacturing order, a delivery ID for identifying the delivery of vials, an acceptance ID for identifying the receipt of vials, a manufacturing location ID for identifying the stem cell manufacturing location, a manufacturing device ID for identifying the manufacturing apparatus, a preservation device ID for identifying the preservation device, and a storage location ID for identifying the storage location where the preservation device is stored. This enables path tracking in case of anomalies at each stage from the acceptance of the stem cell manufacturing order to the preservation of the stem cells. Figure 1 The conveying device 140 shown identifies which fabrication device 101 to which somatic cell collection vial 102 is to be conveyed, based on the fabrication device ID read from the vial. Similarly, the conveying device 141 conveys the fabrication device 101 to the drive device 130 or the drive device 130 to the fabrication device 101, based on the drive device ID read from the vial. Furthermore, the conveying device 142 conveys the stem cell freezing vial 103 to the preservation device 120 based on the preservation device ID read from the vial.

[0077] like Figure 1 As shown, the conveying device 140 further includes a visual sensor 143 for acquiring data. This data is used to input whether the somatic cell collection vial 102 has been introduced into the fabrication device 101 (first state), and the information displaying the acquired first state is sent to the control device 160. Additionally, the conveying device 141 includes a visual sensor 144 for acquiring data. This data is used to input whether the fabrication device 101 is connected to the drive device 130 (second state), and the information displaying the acquired second state is sent to the control device 160. Furthermore, the conveying device 142 includes a visual sensor 145 for acquiring data. This data is used to input whether the stem cell freezing vial 103 can be placed into the preservation device 120 (third state), and the information displaying the acquired third state is sent to the control device 160.

[0078] Other implementations, such as Figure 3B and Figure 4 As shown, the drive device 130 includes switches 153-155 for receiving electrical signals. These electrical signals are used to input at least one of a first state to a third state, and can send information displaying at least one of the first to third states to the control device 160. Further embodiments, such as... Figure 5 As shown, the preservation device 120 includes an in-situ sensor 121 that detects the presence of the stem cell freezing vial 103 for inputting a third state, and can send information displaying the third state to the control device 160. In another embodiment, an input device (not shown) may be included for manually inputting at least one of the first to third states. As the input device, the control device 160, the manufacturing process management terminal (see reference...) can be used. Figure 15 , Figure 16 It includes features such as an LCD touchpad, keyboard, and mouse.

[0079] like Figure 6 As shown, the conveying devices 140 to 142 ( Figure 6 The conveying device (shown only as representative symbol 140) includes a CPU 147 that stores information of at least one of the aforementioned first to third states in a memory 146. In other embodiments, the driving device 130 may include a CPU 132 that stores information of at least one of the aforementioned first to third states in a memory 131. In another embodiment, the storage device 120 may include a CPU 123 that stores information of the aforementioned third state in a memory 122.

[0080] Figure 8This is a flowchart illustrating the operation of the stem cell manufacturing system 100 according to this embodiment, based on the first to third states. When the transport device 140 determines, via the vision sensor 143, that the somatic cell collection vial 102 has not been introduced into the manufacturing device 101 (step S100), it stores information indicating the first state in the memory 146, associating it with the provider ID read from the vial (step S101). Further, when the transport device 141 determines, via the vision sensor 144, that the manufacturing device 101 is not connected to the drive device 130 (step S102), it stores information indicating the second state in the memory 146, associating it with the provider ID read from the vial (step S103). Next, the transport device 140 transports at least one of the somatic cell collection vial 102, the stem cell freezing vial 103, the culture reagent vial 104, and the stem cell manufacturing material vial 105 to the manufacturing device 101 (step S104), and the transport device 141 connects the manufacturing device 101 to the drive device 130 (step S105). Next, when the transport device 142 determines via the vision sensor 145 that the stem cell frozen vial 103 has been discharged from the production device 101 and that the stem cell frozen vial 103 can be placed into the storage device 120 (step S106), it stores the information indicating the third state in the memory 146, associating it with the provider ID read from the vial (step S107). In this way, the transport device 142 transports the stem cell frozen vial 103 to the storage device 120 (step S108).

[0081] like Figure 3AAs shown, the fabrication apparatus 101 includes a separation device 108 for collecting somatic cell collection vials 102 and separating cells from blood, and a drive device 130 includes a pump 133 for transferring a suspension containing separated mononuclear cells within a pre-introduction cell delivery path 109. The fabrication apparatus 101 further includes a factor introduction device 110 comprising an electroporator, which introduces pluripotency-inducing factors into the separated mononuclear cells to create factor-introduced cells. The drive device 130 includes a pump 134 for transferring a solution containing factor-introduced cells within an introduced cell delivery path 111. Additionally, the fabrication apparatus 101 includes an initial culture device 112 for culturing factor-introduced cells, and the drive device 130 includes a pump 135 for transferring a liquid containing cultured stem cell clusters and trypsin-substituted recombinant enzymes within a first cell cluster delivery path 113. Furthermore, the fabrication apparatus 101 includes an expansion culture device 114, which collects a solution containing multiple stem cell clusters separated by mesh or the like in the first cell cluster delivery path 113, distributes it into small wells, and repeatedly expands the culture. The drive device 130 includes a pump 136 that transfers the liquid containing the expanded-cultured stem cell clusters within the second cell cluster delivery path 115. The fabrication apparatus 101 further includes a cell cluster transport mechanism 117 and a packaging device 118. The cell cluster transport mechanism 117 collects a solution containing multiple stem cell clusters separated by mesh or the like in the second cell cluster delivery path 115, and sequentially delivers the separated cell clusters to the pre-packaging cell flow path 116. The packaging device 118 sequentially contains the solution containing multiple stem cell clusters delivered through the pre-packaging cell flow path into stem cell freezing vials 103 and instantaneously freezes them using liquid nitrogen or the like.

[0082] like Figure 4 As shown, the drive device 130 further includes a visual sensor 137 for acquiring data within the fabrication device 101. Based on the data from the visual sensor 137, the status of the stem cells being fabricated as normal is stored as a numerical fourth state in the memory 131. Examples of this fourth state include the size or growth rate of the stem cell clusters in the initial culture device 112 and the expanded culture device 114, the proportion of stem cell cluster sizes, and the hue or pH of the culture reagent.

[0083] Furthermore, the drive unit 130 includes a temperature sensor 138 that detects the temperature within the fabrication apparatus 101. Based on the temperature from the temperature sensor 138, the status of the stem cells being fabricated as normal is stored as a numerical fourth state in the memory 131. Examples of this fourth state include the resistance value and voltage value of the temperature sensor within the initial culture apparatus 112 or the expanded culture apparatus 114.

[0084] In other embodiments, the drive device 130 includes an inspection window (not shown) for visually inspecting the fabrication apparatus 101. Based on the visual inspection performed by the operator through the inspection window, the status of the stem cells being fabricated as a numerical fourth state can be manually input and stored in the memory 131. Examples of this fourth state include the size or growth rate of the stem cell clusters in the initial culture apparatus 112 and the expanded culture apparatus 114, the proportion of stem cell cluster sizes, and the hue of the culture reagent.

[0085] In this embodiment, the drive device 130 further includes an outlet 139 for removing samples discharged from the fabrication device 101. Based on the removed sample, the status of whether the stem cells being fabricated are functioning normally is stored in the memory as a numerical fourth state. Examples of this fourth state include the number of stem cells measured from the sample by a flow cytometer, a cell sorter, etc., the size of the stem cells, the proportion of stem cell cluster sizes, the shape of the stem cells, or the presence or absence of differentiated cells differentiated from the stem cells.

[0086] In another embodiment, the drive unit 130 includes a display device (not shown) for displaying data within the manufacturing apparatus 101. Based on a visual inspection of the displayed data, the normality of the stem cells can be manually input as a numerical fourth state and stored in the memory 131. This fourth state may include, for example, the size or growth rate of the stem cell clusters, the proportion of stem cell cluster sizes, the number of stem cells, the shape of the stem cells, and the hue of the culture reagent. In other embodiments, the display device may be a control device 160 or a manufacturing process management terminal (see [reference]) instead of the drive unit 130. Figure 15 , Figure 16 The driving device 130 further stores at least one of the normal range or abnormal range of the fourth state as first information in the memory 131.

[0087] Figure 9This is a flowchart illustrating the operation of the stem cell manufacturing system 100 according to this embodiment based on the fourth state. When the drive device 130 determines that the stem cells being manufactured are abnormal (i.e., the information indicating the fourth state (e.g., the proportion of stem cell clusters larger than 100 μm after initial culture, or the proportion of stem cell clusters smaller than 30 μm after 14 days) is outside the stored normal range or within the abnormal range (more than 80%)) (step S110), the information indicating the fourth state is associated with the provider ID read from the vial and stored in the memory 131 (step S111). Next, the drive device 130 outputs a first abnormality warning associated with the provider ID and sends it to the portable terminal 180 located at a remote location via the control device 160 and the host computer 170 (step S112). Then, the drive device 130 stops, and the stem cell manufacturing is interrupted (step S113). Next, the drive device 130 cleans the inside of the manufacturing apparatus 101 with a cleaning solution (step S114) and replaces the culture reagent (step S115). Furthermore, the drive device 130 requests the host computer 170 via the control device 160 to reconstruct the production schedule of the production device 101 (step S116). In other embodiments, after the drive device 130 stops in step S113, the transport device 141 can also connect different production devices 101 to the drive device 130 to perform stem cell re-production.

[0088] Figure 10 This is a flowchart illustrating the operation of the stem cell manufacturing system 100 according to this embodiment based on the fourth state. For example... Figure 10 As shown, when the drive device 130 determines that the stem cells being produced are abnormal (i.e., the information indicating the fourth state (e.g., the growth rate of the stem cell clusters in the expanded culture) is outside the stored normal range or within the abnormal range (below 2 μm / h)) (step S120), it stores the information indicating the fourth state in the memory 131 by associating it with the provider ID read from the vial (step S121). Next, the drive device 130 outputs a first abnormality warning associated with the provider ID and sends it to the portable terminal 180 located at a remote location via the control device 160 and the host computer 170 (step S122). Then, the drive device 130 adjusts the amount of culture reagent (e.g., increases the amount of fibroblast growth factor by 5%) (step S123), adjusts the carbon dioxide gas concentration in the initial culture device 112 and the expanded culture device 114 (e.g., increases the CO2 concentration from 5% to 10%) (step S124), and extends the culture time (e.g., extends it by 1 week) (step S125). Furthermore, the drive unit 130 requests the host computer 170 via the control unit 160 to reconstruct the production schedule of the production unit 101 (step S126).

[0089] Refer again Figure 1 Using the vision sensor 143, the conveying device 140 stores the inventory quantity of each vial 102-105 stored in the storage device 150 and the feeding plan of each vial 102-105 as a fifth state in the memory 146, and sends the information representing the fifth state to the control device 160. The control device 160 stores the received information representing the fifth state in the memory 161. In other embodiments, using the vision sensor 151, the storage device 150 can also store the inventory quantity of each vial 102-105 in the storage device 150 and the feeding plan of each vial 102-105 as a fifth state in the memory 152, and send the information representing the fifth state to the control device 160 in a wired or wireless manner.

[0090] Figure 11 This is a flowchart illustrating the operation of the stem cell manufacturing system 100 according to this embodiment based on the sixth state. The control device 160 compares at least one of the information representing the first to fifth states received from the transport devices 140-142, the drive device 130, and the storage device 120 with a predetermined reference state (e.g., a standard operating procedure (SOP)) (step S130), and stores the presence or absence of a difference (sixth state) in memory 161 associating it with the provider ID (step S131). When at least one of the information representing the first to fifth states differs from the predetermined reference state (step S132), the control device 160 outputs a second abnormality warning associated with the provider ID and sends it to a portable terminal 180 located at a remote location via a host computer 170 (step S133). Furthermore, the control device 160 stops the drive device 130 (step S134). In other embodiments, the conveying devices 140-141 may compare the information representing the first and second states with a predetermined reference state (SOP), the storage device 120 may compare the information representing the third state with a predetermined reference state (SOP), or the driving device 130 may compare the information representing the fourth state with a predetermined reference state (SOP). In another embodiment, in the aforementioned steps S130-S131, the control device 160 may not compare the first to fifth states, but instead compare the operation item with the SOP to determine whether other operation items are running correctly, and store the presence or absence of differences in memory 161 in association with the provider ID.

[0091] Figure 5This is a perspective view of the preservation apparatus according to this embodiment. The preservation apparatus 120 includes: a receiving portion 124 for accommodating one or more stem cell freezing vials 103, a freezing tank 125 for accommodating a cold-keeping medium (e.g., liquid nitrogen with a liquid phase of -180°C or below and a gas phase of -160°C or below) for cryopreserving the stem cell freezing vials 103 and which is vacuum insulated, and a supply valve 126 for pre-supplying the cold-keeping medium.

[0092] The storage device 120 further includes a visual sensor 127 for acquiring data within the storage device 120. Based on the data from the visual sensor 127, the status of the preserved stem cells as a numerical seventh state is stored in the memory 122 (see reference). Figure 6 As for this seventh state, examples include the presence or absence of stem cells (or the presence or absence of freezing solution) in the stem cell freezing vial 103.

[0093] Additionally, the preservation device 120 includes a temperature sensor 128 for detecting the temperature within the preservation device 120. Based on the temperature from the temperature sensor 128, the condition of the preserved stem cells as a numerical seventh state is stored in the memory 122. This numerical seventh state can include the resistance value, voltage value, and temperature obtained from the temperature sensor. The stem cells are preferably kept at a temperature below -160°C, as temperature changes of around 20°C can cause significant damage or death.

[0094] Furthermore, the preservation device 120 includes a cold medium remaining amount sensor 129 for detecting the remaining amount of cold medium within the preservation device 120. Based on the remaining amount from the cold medium remaining amount sensor 129, the condition of the preserved stem cells as normal is stored in the memory as a numerical seventh state. Examples of this seventh state may include the voltage value and resistance value of the remaining amount sensor. The preservation device 120 further stores at least one of the normal range and abnormal range of the seventh state as second information in the memory 122.

[0095] Figure 12 This is a flowchart illustrating the operation of the stem cell manufacturing system 100 according to this embodiment based on the seventh state. When the storage device 120 determines that the stored stem cells are abnormal (i.e., the information indicating the seventh state (e.g., the temperature from the temperature sensor) is outside the stored normal range or within an abnormal range (above -160°C)) (step S140), the information indicating the seventh state is associated with the provider ID read from the vial and stored in the memory 122 (step S141). Next, the storage device 120 outputs a third abnormality warning associated with the provider ID and sends it to the portable terminal 180 located at a remote location via the control device 160 and the host computer 170 (step S142).

[0096] Figure 13 This is a flowchart illustrating the operation of the stem cell manufacturing system 100 according to this embodiment based on the eighth state. The control device 160 stores at least one (eighth state) of the actual operation records of the transport devices 140-142, the drive device 130, and the storage device 120, associated with a provider ID, in the memory 161 (step S150). Next, the control device 160 compares the eighth state with a predetermined reference state (e.g., a standard operating procedure (SOP)) (step S151), and stores the presence or absence of a difference (sixth state) associated with the provider ID in the memory 161 (step S152). When the eighth state differs from the predetermined reference state (step S153), the control device 160 outputs a second abnormal warning associated with the provider ID and sends it via a host computer 170 to a remote portable terminal 180 (step S154). In other embodiments, the conveying devices 140-142, the driving device 130, and the storage device 120 may store their respective actual operation records (eighth state) associated with the provider ID, compare the eighth state with a predetermined reference state (SOP), and store the presence or absence of differences (sixth state) associated with the provider ID in the memory 161.

[0097] The memory storing at least one of the aforementioned first to eighth states can be a single unit, i.e., a single memory possessed by the control device 160 and the host computer 170. Furthermore, at least one of the first to eighth states can be wirelessly transmitted to a portable terminal 180 located at a remote distance.

[0098] Figure 7 This is a functional block diagram of the site system applied in the stem cell manufacturing system 100 according to this embodiment. The stem cell manufacturing system 100 further includes: a control device 160 equipped with interface software 163 and working software 164, and an input device connected to the control device 160 via wired or wireless connection for inputting information during the manufacturing process. Examples of input devices include the aforementioned drive device 130, storage device 120, and transport devices 140-142. In other embodiments, examples include input devices for manually inputting information representing at least one of the first to eighth states.

[0099] The control device 160 continuously inputs current values ​​of pumps 1 to 4, voltage values ​​of switches 1 to 3, and data from vision sensors from one or more drive devices 130, and continuously inputs resistance values ​​of temperature sensors, temperature data from temperature estimation units, impedance of somatic cell coagulation monitoring devices, voltage values ​​of cold medium remaining quantity sensors, and data from vision sensors from one or more storage devices 120, and continuously inputs current values ​​of servo motors of each axis and data from vision sensors from the conveying device 140. Because information inherent to various components from multiple input devices is continuously sent out, it is not easy to determine, for example, the flow rate of which pump is operating in which drive device or manufacturing device. Therefore, the interface software 163 converts information constructed in the data format inherent to the input devices into information constructed in the data format inherent to the operating software 164. The data format inherent to the operating software 164 is constructed using a data model with a tree or network data structure representing the hierarchical relationships of the components of each input device, and various data models are pre-stored in the memory 161 of the control device 160. For ease of understanding, information inherent to input devices, such as the current value of the first pump of drive unit 130, is converted into a structured data format inherent to the operating software, such as drive unit ID / manufacturing device ID / first pump / current value / flow rate. Through this conversion process, the operating software 164 can instantly utilize the data inherent to multiple components from multiple input devices.

[0100] According to the aforementioned stem cell manufacturing system 100, multiple closed-loop manufacturing devices 101 can simultaneously and in parallel produce large quantities of stem cells from multiple recipients. Furthermore, the closed-loop FA system, which eliminates the need for cleanrooms, enables cost reduction, high-level quality control, contamination prevention, and the elimination of manpower shortages. Additionally, the application of a site system can shorten production time. Moreover, the stem cell manufacturing system 100 prevents cross-contamination with other people's somatic cells or stem cells by reading various identification information assigned to each vial. The stem cell manufacturing system 100 can make a significant contribution, particularly to the development of the clinical iPS cell industry.

[0101] 2. Stem Cell Information Management System

[0102] Figure 14This is a schematic diagram illustrating the server-type configuration of the stem cell information management system 200 in this embodiment. The stem cell information management system 200 includes a server device 201 located in the cloud and is composed of a cloud system that centrally manages big data in the following processes: accepting manufacturing orders for stem cells made from somatic cells; transporting somatic cells collected from somatic cell providers or stem cells made from somatic cells; examining somatic cells or stem cells; manufacturing processes for making stem cells from somatic cells; and storing stem cells. This server device 201 corresponds to the host computer 170 shown in other figures. In this embodiment, a system for making iPS cells from blood cells has been described, but it is understood that it can also be applied to systems for making iPS cells from skin cells or systems for making ES cells from embryonic cells, etc. First, an overview of the processing performed by the stem cell information management system 200 will be described.

[0103] During the acceptance process, when accepting a stem cell manufacturing request, the server device 201 determines the entire schedule from the acceptance process to the storage process according to the method of making stem cell production in the shortest path and in the shortest time. Upon acceptance, the server device 201 stores provider information, including at least one of the following: informed consent form from the somatic cell provider, nationality, address, gender, age, blood type, past medical records, prescription records, health diagnosis results, and information on family members who have previously produced stem cells, associated with a provider ID in the storage unit 202. Next, a collection kit 209, containing at least one or more somatic cell collection vials 102 assigned a provider ID, is specifically sent to the somatic cell provider to prevent confusion with other people's somatic cells or stem cells, and errors in the correspondence of provider IDs. In other embodiments, the collection kit 209 can be sent not only to the somatic cell provider but also in advance to the somatic cell collection institution. The somatic cell collection vial 102 is equipped with an individual identification device 106, which, in addition to containing the provider ID, also includes... Figure 2 At least one of the following: order ID, delivery ID, receiving ID, manufacturing location ID, manufacturing device ID, storage device ID, and storage location ID.

[0104] In the somatic cell delivery process, one or more somatic cell collection vials 102 are placed into a delivery container 250. The delivery container 250 is transported from the collection facility to the inspection facility, and from the inspection facility to the stem cell manufacturing site, using a delivery vehicle comprising at least one of automobiles, railways, aircraft, ships, and automated devices. During delivery, information such as temperature, cumulative delivery time, vibration, and the coagulation state of the somatic cells within the delivery container 250 is sent to a server device 201, which issues anomaly warnings and schedule corrections.

[0105] In the somatic cell examination process, the collected somatic cells undergo virus or bacterial testing, blood cell count measurement, and gene expression level measurement. During the examination, the results are sent to server device 201, which issues warnings for abnormalities and makes schedule corrections. Specifically, server device 201 is characterized by the following: based on previously accumulated data regarding the donor's age, past medical history, presence or absence of family members who have previously undergone stem cell production, blood cell count, and the presence and level of specific gene expression, and the correlation between these data and the somatic cell reprogramming (initialization) rate, it determines the predicted reprogramming rate as an indicator of whether somatic cell reprogramming is feasible, and issues warnings for abnormalities and makes schedule corrections.

[0106] During the manufacturing process, information representing the first to eighth states in the aforementioned stem cell manufacturing system 100 is sent to the server device 201, which then issues anomaly warnings and schedule corrections. Additionally, upon acceptance, if the stem cell frozen vial 103 cannot be discharged from the manufacturing device 101 according to the initially set expected discharge date and time by the server device 201, anomaly warnings are issued and schedule corrections are performed.

[0107] In the stem cell delivery process, stem cell freezing vials 103 containing stem cells produced at the stem cell manufacturing site are placed into a delivery container 250 and transported by a transport vehicle including at least one of automobiles, railways, aircraft, ships, and automated devices. The delivery container 250 includes a preservation device 120 utilizing the aforementioned cold-insulating medium; however, the cold-insulating medium within the preservation device 120 is discharged from a safety valve over time, thus the preservation device 120 only has a short-term preservation function. During delivery, information such as not only the temperature within the preservation device 120, cumulative delivery time, and vibration, but also the remaining amount of cold-insulating medium or the remaining amount of pre-prepared cold-insulating medium is sent to a server device 201, which then issues anomaly warnings and schedule corrections.

[0108] During the storage process, one or more storage devices 120 are stored in the reservoir of the stem cell storage location, and a cooling medium is stably supplied to the one or more storage devices 120. Therefore, the stem cell storage location has a long-term storage function. During storage, in addition to the temperature inside the storage device 120 and the remaining amount of cooling medium, the presence or absence of stem cells (or the presence or absence of freezing solution) is also sent to the server device 201, which issues anomaly warnings and schedule corrections.

[0109] The stem cell examination process includes genomic information checks and HLA classification checks of somatic cells and stem cells. During the examination, the results are sent to server device 201, which issues warnings for abnormalities and makes schedule corrections. Specifically, server device 201 is characterized by: determining whether somatic cells and stem cells originate from the same individual based on their genomic information and HLA type, and issuing warnings for abnormalities and making schedule corrections.

[0110] Figure 15 This is a block diagram illustrating the server-type configuration of the stem cell information management system 200 according to this embodiment. The server device 201 includes a storage unit 202 and a determination unit 203. The storage unit 202 stores the collection schedule of somatic cells from a somatic cell provider, the inspection schedule of the somatic cells, the production schedule of one or more closed-loop production devices for producing stem cells from somatic cells, the storage schedule of one or more storage devices for cryopreserving the produced stem cells, and the storage schedule of the storage location for storing the storage devices. The determination unit 203, based on the stored collection schedule, inspection schedule, production schedule, storage schedule, and storage schedule, determines, upon receiving an application, a schedule for stem cell production using the shortest path and in the shortest time. In other embodiments, the determination unit 203 may also determine the schedule based on the supply schedule of culture reagents and materials for stem cell production.

[0111] like Figure 15 As shown, the stem cell information management system 200 further includes an order management terminal 210 connected to the server device 201 via wired or wireless connection for accepting orders for somatic cell manufacturing, an acceptance management terminal 220 for managing the acceptance of somatic cells, a manufacturing process management terminal 230 for managing the manufacturing process, and a storage management terminal 240 for managing the storage of stem cells. The acceptance management terminal 220 pre-stores the collectable dates in the collection facility and the inspectable dates in the inspection facility in the storage unit 211, and the storage management terminal 240 pre-stores the available storage locations and storage periods of the stem cell storage locations in the storage unit 241. In this embodiment, these terminal devices 210-240 are configured in... Figure 14 The stem cell manufacturing site shown is in another location, or it can be configured as a single frame, in other embodiments.

[0112] Figure 17This is a sequence diagram illustrating the server-type operation of the stem cell information management system 200 according to this embodiment. The server device 201 receives in advance the collectable dates of collectable somatic cells and the examineable dates of examineable somatic cells from the receiving management terminal 220 and stores them in the storage unit 202 (step S200). In other embodiments, the server device 201 receives the collectable dates directly from the collection institution and the examineable dates directly from the inspection institution. The server device 201 further receives in advance the production time periods of one or more closed-loop manufacturing devices 101 from the manufacturing process management terminal 230 and stores them in the storage unit 202 (step S201). Additionally, the server device 201 receives in advance the storage location and storage time periods from the storage management terminal 240 and stores them in the storage unit 202 (step S202). In other embodiments, the server device 201 can directly receive the storage location and storage time periods from the storage location.

[0113] If the server device 201 receives a manufacturing request containing the desired collection date and a provider ID from the order management terminal 210 simultaneously (step S203), it determines the somatic cell collection date based on whether the desired collection date matches a stored available collection date (step S204). The server device 201 further determines the delivery date by delivering the collection kit 209 7 days before the determined collection date (step S205). In addition, the server device 201 determines the somatic cell inspection date based on whether the date obtained by adding 2 days to the determined collection date to the somatic cell delivery period matches a stored available inspection date (step S206). The server device 201 further determines the somatic cell acceptance date at the stem cell manufacturing site based on whether the date obtained by adding 7 days to the somatic cell inspection period and 2 days to the somatic cell delivery period is within the available manufacturing period of one or more stored closed manufacturing devices 101 (step S207). In addition, the server device 201 determines the stem cell manufacturing period in a way that stem cell manufacturing can begin immediately from the determined somatic cell acceptance date (step S208). That is, the server device 201 determines the stem cell production period based on the determined somatic cell collection date and the production period of one or more stored closed production devices 101. Upon acceptance, the server device 201 initially sets the expected discharge date and time of the stem cell frozen vial 103 discharged from the closed production device 101 to 3 months after the production start date. Furthermore, the server device 201 determines the storage period based on whether the expected discharge date and time of the stem cell frozen vial 103 is within the storage period of one or more storage devices 120 (step S208). Next, the server device 201 determines the stem cell storage location and storage period based on whether the date obtained by adding 4 days of cell delivery time to the expected discharge date and time of the stem cell frozen vial 103 is within the storage period of the nearest storage location among the stored storage locations (step S209). The server device 201 determines the shipment date of the produced stem cells based on the determined production period and the stored storage location and storage period (step S210). The server device 201 stores the determined somatic cell collection date, collection kit 209 delivery date, somatic cell inspection date, somatic cell acceptance date, stem cell production period, stem cell preservation period, stem cell storage location and preservation period, and stem cell shipment date in the storage unit 202 along with the provider ID (step S211), and sends it to the somatic cell provider indicated by the provider ID (step S212). In other embodiments, the server device 201 may determine the preservation period for temporarily storing the somatic cells after determining the somatic cell acceptance date in step S207. For example, the preservation period may include the period for preserving peripheral blood mononuclear cells separated from blood.

[0114] Reference Figures 19-22 This explains the details of the schedule determination in steps S204 to S211. Figures 19-22 This diagram illustrates the associated database of the following tables stored in the storage unit, which includes server device 201: provider scheduling table 500, acquisition agency scheduling table 501, inspection agency scheduling table 502, manufacturing location scheduling table 503, production device scheduling table 504, storage device scheduling table 505, order receiving table 506, acceptance table 507, production table 508, storage table 509, storage location scheduling table 510, and storage table 511. The following section addresses... Figure 21 This section explains the case where the order ID in order table 506 is 0001. In step S204, [the text abruptly ends here]. Figure 19 The nearest collection location for the address of provider ID 0102 in provider scheduling table 500 is... Figure 19 The data collection agency ID in the data collection agency scheduling table 501 is 0001, and... Figure 21 The second expected collection date for order form 506 is March 16, 2018. Figure 19 The first collectable day, 2018 / 03 / 16, is consistent with the collection agency scheduling table 501. Therefore, the server device 201 determines 2018 / 03 / 16 as the somatic cell collection day.

[0115] In step S205, server device 201 will act as Figure 21 The date 2018 / 03 / 09, which is 7 days before the somatic cell collection date of 2018 / 03 / 16 in order form 506, is determined as the delivery date of collection kit 209. In step S206, the date 2 days before the somatic cell collection date of 2018 / 03 / 16 is added to the somatic cell delivery period, resulting in 2018 / 03 / 18. Figure 19 The second available inspection date of the nearest inspection agency in the inspection agency scheduling table 502 is consistent with 2018 / 03 / 18, therefore the server device 201 determines 2018 / 03 / 18 as the somatic cell examination date. In step S207, the... Figure 21 The order form 506 shows a somatic cell examination date of 2018 / 03 / 18, which, when combined with a 7-day somatic cell examination period and a 2-day somatic cell delivery period, results in a date of 2018 / 03 / 27. Figure 22 The manufacturing location ID in manufacturing table 508 is 0001, and it is within its manufacturing period from 2018 / 03 / 16 to 2018 / 09 / 16, therefore... Figure 21 As shown in Acceptance Table 507, server device 201 designated 2018 / 03 / 27 as the somatic cell acceptance date.

[0116] However, when Figure 21When the order ID in order form 506 is 0003, the date after adding 7 days for the somatic cell examination period and 2 days for the somatic cell delivery period to the somatic cell examination date of 2018 / 03 / 27 is 2018 / 04 / 05. Figure 22 The manufacturing location ID for production table 508 is 0003, and it is not within its production period, therefore... Figure 22 As shown in Table 508, server device 201 issues a warning for schedule rescheduling and prompts the user to inquire with the somatic cell provider about alternative desired collection dates.

[0117] Returning to the case where the order ID is 0001, in step S208, as follows... Figure 22 As shown in Table 508, following the method of directly starting stem cell production from the somatic cell acceptance date of March 27, 2018, the server device 201 designated March 27, 2018 to September 16, 2018 as the production period. In step S209, the server device 201 will... Figure 22 The estimated discharge date and time for the frozen stem cell vials are pre-set to 2018 / 06 / 27, three months after the start date of production (March 27, 2018). The estimated discharge date and time of 2018 / 06 / 27 is included in... Figure 20 The storage device schedule 505 shows the storage period from 2018 / 06 / 18 to 2018 / 07 / 17, therefore, if Figure 22 As shown in the storage table 509, the server device 201 has determined the period from 2018 / 06 / 27 to 2018 / 07 / 17 as the storage period.

[0118] However, when Figure 22 When the order ID for production table 508 is 0002, the estimated production date and time 2018 / 07 / 02 is not present. Figure 20 The storage device scheduling table 505 shows the storage period with manufacturing location ID 0002, therefore, as Figure 22 As shown in the saved table 509, the server device 201 issues a warning for schedule readjustment, prompting the user to inquire with the somatic cell provider about alternative desired collection dates.

[0119] Returning to the case where the order ID is 0001, in step S210, ... Figure 22 The estimated production date and time is June 27, 2018, plus a 4-day delivery period, and the date 4 days later is July 1, 2018. Figure 22The storage location schedule 510 shows that the nearest available storage location in LA has a storage period from June 16, 2018. Therefore, server device 201 determines the LA storage location and the 50-year period starting from July 1, 2018 as the storage location and storage period. In step S211, server device 201 determines the expected discharge date and time, June 27, 2018, as the shipment date for the stem cells.

[0120] Figure 16 This is a block diagram illustrating a media-utilization configuration of a stem cell information management system 260 according to another embodiment. The stem cell information management system 260 differs from the server-type configuration in that it does not use a server device 201, but its other configurations are the same as the server-type configuration. The stem cell information management system 260 transmits various information between the terminal devices 210-240 via paper media or communication media. Since the stem cell information management system 260 does not use a server device 201 on the cloud, it offers excellent security and helps prevent the leakage of personal information. The stem cell information management system 260 includes an order management terminal 210, an order receiving management terminal 220, a manufacturing process management terminal 230, and a storage management terminal 240 that are interconnected via wired or wireless connections. Each terminal device 210-240 has a unit for determining various information such as schedules 212, 222, 232, 242, and a storage unit 211, 221, 231, 241 for storing various data.

[0121] Figure 18 This is a sequence diagram illustrating the operation of the stem cell information management system 260. The receiving management terminal 220 pre-stores the collectable dates of the collection institution and the inspectable dates of the inspection institution in the storage unit 221 (step S220), outputs the collectable dates and inspectable dates to the second medium, and transmits them to the order receiving management terminal 210 (step S221). The manufacturing process management terminal 230 pre-stores the manufactureable time period of the manufacturing device in the storage unit 231 (step S222), outputs the manufactureable time period to the third medium (step S223), and transmits it to the receiving management terminal 220 (step S224). The storage management terminal 240 pre-stores the storeable location and storeable time period of the storage location in the storage unit 241 (step S225), outputs the storeable location and storeable time period to the fifth medium (step S226), and transmits it to the manufacturing process management terminal 230 (step S227).

[0122] After receiving a manufacturing request containing the desired collection date and the provider ID (step S228), the order management terminal 210 determines the somatic cell collection date based on whether the desired collection date matches the collection date conveyed by the second media (step S229). The order management terminal 210 further determines the delivery date by delivering the collection kit 209 7 days before the determined collection date (step S229). In addition, the order management terminal 210 determines the somatic cell inspection date based on whether the date obtained by adding 2 days to the determined collection date matches the inspection date conveyed by the second media (step S229). The order management terminal 210 outputs the determined collection date and inspection date to the first media (step S230) and conveys them to the receiving management terminal 220 and the manufacturing process management terminal 230 (step S231).

[0123] The receiving management terminal 220 determines the somatic cell acceptance date based on whether the date obtained by adding a 7-day somatic cell examination period and a 2-day somatic cell delivery period to the examination date transmitted by the first media falls within the production period transmitted by the third media (step S232). That is, the receiving management terminal 220 determines the somatic cell acceptance date based on the determined collection date and the production period transmitted by the third media.

[0124] The manufacturing process management terminal 230 determines the somatic cell acceptance date using the same processing procedure as the order management terminal 210 (step S233). Furthermore, the manufacturing process management terminal 230 determines the stem cell production period by directly starting stem cell production from the determined somatic cell acceptance date (step S234). That is, the manufacturing process management terminal 230 determines the stem cell production period based on the somatic cell collection date and the stored production period communicated by the first media. The manufacturing process management terminal 230 further sets the expected discharge date and time of the stem cell frozen vial discharged from the sealed production device to three months after the production start date, and determines the storage period based on whether the expected discharge date and time are within the storage period of the storage device (step S234). Next, the manufacturing process management terminal 230 determines the stem cell shipment date based on whether the date obtained by adding four days of stem cell delivery time to the expected discharge date and time is within the storage period of the nearest storage location among the storage locations communicated by the fifth media (step S234). That is, the manufacturing process management terminal 230 determines the shipment date of the stem cells based on the stem cell production period and the storage location and storage period transmitted by the fifth media. The manufacturing process management terminal 230 outputs the determined production period and storage period to the fourth media (step S235) and transmits them to the storage management terminal 240 (step S236).

[0125] The storage management terminal 240 determines the storage location and storage period of the stem cells using the same processing procedure as the manufacturing process management terminal 230 (step S237). That is, the storage management terminal 240 determines the storage location and storage period of the stem cells based on the stem cell production period communicated by the fourth medium and the stored storage location and storage period.

[0126] The order management terminal 210 associates the determined collection date, reagent kit delivery date, and somatic cell examination date with the provider ID and stores them in the storage unit 211, and sends them to the provider (step S239). Similarly, the receiving management terminal 220 associates the determined somatic cell acceptance date with the provider ID and stores it in the storage unit 221, and sends it to the provider (step S240). Similarly, the manufacturing process management terminal 230 associates the determined manufacturing period, storage period, and shipping date with the provider ID and stores them in the storage unit 231, and sends them to the provider (step S241). The storage management terminal 240 associates the determined storage location and storage period with the provider ID and stores them in the storage unit 241, and sends them to the provider (step S242).

[0127] According to the stem cell information management system 200 and 260, whether it is a server-type configuration or a media-type configuration, when a manufacturing order is accepted, the determination unit of the server device 201 or the terminal devices 210-240 determines the stem cell production schedule with the shortest path and the shortest time, thus enabling the reduction of production time and high-quality management.

[0128] The following section explains the schedule correction for abnormalities in the delivery, inspection, and manufacturing processes, based on a stem cell information management system 200 configured with a server. Figures 23-27 This diagram illustrates the structure and operation of the stem cell information management system 200 during the delivery process. (See diagram for example.) Figure 23 As shown, the stem cell information management system 200 further includes a delivery container 250 configured to hold one or more somatic cell collection vials. The delivery container 250 includes at least one of the following: a heating / cooling device 253 connected to a temperature sensor 251 and a heating / cooling module 252; a cumulative time measuring device 254 for measuring the cumulative delivery time of the delivery container 250; a somatic cell coagulation monitoring device 255 for monitoring the coagulation state of the somatic cells in the somatic cell collection vials; and a vibration monitoring device 256 for monitoring the vibration of the delivery container 250. The delivery container 250 further includes a memory 275 for storing various data, a communication control unit capable of wirelessly communicating with a host computer, and a CPU 258 for controlling the entire delivery container 250.

[0129] like Figure 24As shown, the heating and cooling device 253 includes a temperature estimation unit 259 that estimates the temperature of somatic cells located in the delivery container 250, and a heating and cooling unit 261 that automatically heats or cools the cells in a manner that is linked to temperature data from the temperature estimation unit to maintain the temperature at a constant level. The temperature estimation unit 259 estimates the temperature of the somatic cells based on the temperature from the temperature sensor 251 and the thermal conductivity of the somatic cell collection vial 102. The heating and cooling unit 261 outputs current to the heating and cooling module 252 when the temperature data from the temperature estimation unit 259 reaches a target temperature (e.g., 4°C). Furthermore, the heating and cooling device 253 stores an upper limit temperature and a lower limit temperature, and outputs an abnormal temperature warning when the temperature data from the temperature estimation unit 259 is above the upper limit temperature or below the lower limit temperature.

[0130] Although not illustrated, the cumulative time measuring device 254 is equipped with a timer device having start and stop functions, and measures the cumulative transport time starting from the date and time of somatic cell collection or the date and time of discharge from the stem cell frozen vial 103. Furthermore, the cumulative time measuring device 254 stores the time during which the somatic cells or stem cells can maintain their quality, and outputs an abnormal time warning when the cumulative transport time exceeds the time during which the quality can be maintained.

[0131] like Figure 25 As shown, the somatic cell coagulation monitoring device 255 includes an alternating current generating unit 276 that generates alternating current, an impedance measuring unit 277 that measures impedance from the alternating current applied to somatic cells, and a somatic cell coagulation monitoring unit 278 that monitors the coagulation state of somatic cells based on pre-stored correlation data between impedance and somatic cell coagulation state. The somatic cell coagulation monitoring device 255 stores upper and lower limits of values ​​that quantify the coagulation state (e.g., impedance or somatic cell coagulation value obtained from impedance), and outputs an abnormal coagulation warning when the somatic cell coagulation value is above the upper limit or below the lower limit.

[0132] The vibration monitoring device 256 is equipped with a vibration sensor 257 that detects the vibration of the conveying container 250 (displacement, velocity, acceleration or force in three dimensions). When the value of the vibration from the vibration sensor 257 (e.g., a value related to the total energy of the vibration, or a value obtained by integrating the absolute value of the acceleration relative to the time axis) exceeds the upper limit, an abnormal vibration warning is output.

[0133] Figure 26 To represent the diagram of transport table 512 that contains transport information, Figure 27This diagram illustrates the operation of the stem cell information management system 200 based on delivery information. The delivery container 250 stores delivery information, including at least one of the aforementioned temperature data, cumulative delivery time, a value representing the coagulation state, and a value representing vibration, in memory 275, associated with at least a provider ID, and sends it to a server device 201, which acts as a host computer 170 (step S230). When at least one of the temperature data (step S231), cumulative delivery time (step S232), a value representing the coagulation state (step S233), and a value representing vibration (step S234) is outside the normal range, the server device 201 determines the output of a delivery anomaly warning and schedule correction (step S235), and sends the delivery anomaly warning and delivery information to a portable terminal 180 located at a remote location (step S236).

[0134] Figures 28-30 This diagram illustrates the structure and operation of the stem cell information management system 200 during the somatic cell examination process. (See diagram for details.) Figure 28 As shown, the stem cell information management system 200 further includes a first inspection device 285 for checking whether the collected somatic cells are easily reprogrammable. The first inspection device 285 includes at least one of a somatic cell count measuring device 286 for measuring the number of somatic cells (e.g., the number of T cells, NK cells, B cells, etc. relative to 1 ml of blood) and a gene expression level measuring device 287 for measuring the expression level of a specific gene. The first inspection device 285 further includes a memory 288 for storing various data, a communication control unit 289 capable of wireless or wired communication with a server device 201 (which serves as a host computer), and a CPU 290 for controlling the entire first inspection device 285. The measured somatic cell count and the presence or absence of expression of a specific gene, or the expression level, are associated with a provider ID and stored in the memory 288, and then sent to the server device 201 (which serves as a host computer 170). In other embodiments, the first inspection device 285 may include an HLA-type device, a genome information inspection device for checking genomic information, etc.

[0135] like Figure 29 As shown, the server device 201, serving as the host computer 170, further includes a multivariate regression analysis unit 204 and a reprogramming prediction rate determination unit 205. The multivariate regression analysis unit 204 stores the correlation data between various previously accumulated data and the reprogramming rate in the storage unit 202 and performs multivariate regression analysis based on the correlation data. The reprogramming prediction rate determination unit 205 determines the reprogramming prediction rate of the somatic cell provider. In other embodiments, the first inspection device 285 may include the multivariate regression analysis unit 204 and the reprogramming prediction rate determination unit 205, and send the reprogramming prediction rate, which is an indicator of whether the somatic cells are easy to reprogram, to the server device 201.

[0136] In another embodiment, the server device 201 may include a machine learning unit and a reprogramming prediction rate determination unit. The machine learning unit learns features or patterns of data based on various combinations of previously accumulated data and reprogramming rates, and the reprogramming prediction rate determination unit determines the reprogramming prediction rate based on the learned features or patterns of the data. In a further embodiment, the server device 201 may include a neural network generation unit that generates a neural network based on various combinations of previously accumulated data and reprogramming rates, and a reprogramming prediction rate determination unit that determines the reprogramming prediction rate based on the generated neural network. Furthermore, it is understood that deep learning and AI can be utilized in determining the reprogramming prediction rate.

[0137] like Figure 30 As shown, the server device 201 stores the examination information from the first examination device (i.e., somatic cell count, presence and level of expression of specific genes. In other embodiments, it may also include HLA type, genomic information, SNP, etc.) in the storage unit 202, at least associated with the provider ID (step S240). Next, the server device 201 determines the reprogramming prediction rate based on the stored provider's age, past medical history, information on family members who have previously produced stem cells, somatic cell count, and presence and level of expression of specific genes. When the reprogramming prediction rate is not within the normal range (e.g., less than 50%) (step S241), it determines the output of an abnormal warning during the examination and schedule correction (step S242), and sends the abnormal warning and examination information to the portable terminal 180 located at a remote location (step S243).

[0138] Figures 31-33 This is a flowchart illustrating the operation of the stem cell information management system 200 during the manufacturing process. The stem cell information management system 200 further includes a transfer device 140 and a server device 201. The transfer device 140, based on the manufacturing device ID read from the vials, transfers at least one of the following to the manufacturing device 101: somatic cell collection vial 102, stem cell freezing vial 103 (empty vial), stem cell preparation material vial 105, and culture reagent vial 104 (see reference). Figure 1 The server device 201 stores inventory information for the stem cell preparation material vials 105 and culture reagent vials 104.

[0139] like Figure 31As shown, when the server device 201 determines that the production period of the production device 101, as determined at the time of acceptance, has begun (step S250), the transport device 140 determines whether a somatic cell collection vial 102 exists (step S251). If a somatic cell collection vial 102 exists, the server device 201, based on the stored inventory information of stem cell production materials and culture reagents (step S252), determines to use the transport device 140 to transport at least one of the stem cell production material vial 105 and the culture reagent vial 104. Based on the production device ID read from the vial, the transport device 140 transports the somatic cell collection vial 102, the stem cell freezing vial 103 (empty vial), the stem cell production material vial 105, and the culture reagent vial 104 to the production device 101 (step S253). However, when there is no somatic cell collection vial 102, or when there is no stock of at least one of stem cell freezing vial 103 (empty vial), stem cell preparation material vial 105, and culture reagent vial 104, the server device 201 determines the output of an abnormal warning during production and schedule correction (step S254), and sends the abnormal warning during production to a portable terminal located at a distance (step S255).

[0140] like Figure 32 As shown, the stem cell information management system 200 further includes a visual sensor (e.g., for acquiring data within the fabrication apparatus 101) to obtain data. Figure 6 The server device 201 stores data from the visual sensor 137 in the storage unit 202 (step S260). Based on the stored data from the visual sensor 137, the server device 201 determines whether the size or growth rate of the stem cell cluster is within the normal range (step S261), whether the number of stem cells is within the normal range (step S262), whether the shape of the stem cells is within the normal range (step S263), whether the hue or pH of the culture reagent is within the normal range (step S264), and whether differentiated cells differentiated from stem cells are present (step S265). When these production information are not within the normal range, the server device 201 outputs an abnormality warning during production and corrects the schedule (including correction of the expected discharge date and time) (step S266), and sends the abnormality warning and production information to the portable terminal 180 located at a remote location (step S267).

[0141] like Figure 33As shown, further, when the server device 201 determines that it is 10 minutes before the expected discharge date and time of the stem cell frozen vial 103 determined at the time of acceptance (step S270), the transfer device 142 starts to detect the discharge of the stem cell frozen vial 103 using the vision sensor 145 (step S271). When the transfer device 142 detects the discharge of the stem cell frozen vial 103 (step S272), the transfer device 142 transfers the stem cell frozen vial 103 to the storage device 120 (step S273). However, if the discharge of the stem cell frozen vial 103 is not detected within the expected discharge date and time (step S274), the detection is repeated until 10 minutes have elapsed from the expected discharge date and time. If 10 minutes have elapsed, the server device 201 outputs an abnormality warning during production and corrects the schedule (step S275), and sends the abnormality warning and production information to the portable terminal 180 located at a remote location (step S276).

[0142] Figures 34-37 This diagram illustrates the structure and operation of the stem cell information management system 200 in the stem cell examination process. (See diagram for details.) Figure 34 As shown, the stem cell information management system 200 further includes at least one of a second inspection device 291 having a genome information inspection device 279 for somatic cells and stem cells, and a third inspection device 295 having an HLA typing device 280 for inspecting the HLA types of somatic cells and stem cells. The second inspection device 291 or the third inspection device 295 further includes a memory 292, 296 for storing various data, a communication control unit 293, 297 capable of wireless or wired communication with a server device 201 acting as a host computer, and a CPU 294, 298 for controlling the second inspection device 291 or the third inspection device 295 as a whole. The measured genome information or the measured HLA type of somatic cells and stem cells is associated with a provider ID read from a vial and stored in the memory 292, 296, and then sent to the server device 201 acting as a host computer 170. In other embodiments, the stem cell information management system 200 may include both the second inspection device 291 and the third inspection device 295. In further embodiments, the stem cell information management system 200 may include a fourth inspection device for examining the SNPs or genomic sequences of somatic cells and stem cells.

[0143] like Figure 35 and Figure 36As shown, the server device 201, serving as the host computer 170, further includes an identity determination unit 206 that determines whether the genomic information of somatic cells and stem cells are the same or whether the HLA types of somatic cells and stem cells are the same. In other embodiments, the identity determination unit 206 may be provided not by the server device 201, but by a second inspection device 291 or a third inspection device 295. In another embodiment, the server device 201 may include an identity determination unit that determines whether SNPs or genomic sequences are the same.

[0144] like Figure 37 As shown, the server device 201 stores the inspection information (i.e., the genomic information or HLA type of somatic cells and stem cells) from the second inspection device 291 or the third inspection device 295 in the storage unit 202, associating it with the provider ID read from the vial (step S280). Next, when the genomic information or HLA type of somatic cells and stem cells is different (step S281), the server device 201 determines the output of an abnormal warning during inspection and schedule correction (step S282), and sends the abnormal warning and inspection information to the portable terminal 180 located at a remote location (step S283).

[0145] Figure 38 This is a functional block diagram of the site system applied in the stem cell information management system 200 according to this embodiment. The stem cell information management system 200 further includes a control device 284 having interface software 282 and working software 283, and an input device connected to the control device 284 via wired or wireless connection for inputting information for each process. Examples of input devices include the aforementioned delivery container 250, first inspection device 285, and drive device 130. In other embodiments, an input device for manually inputting information for each process may be included.

[0146] The control device 284 continuously inputs, for example, the first current value of the forward-scattered light and the second current value of the backscattered light of the first to third cell sorters from the first inspection device 285; continuously inputs temperature data from the temperature estimation unit, impedance of the somatic cell coagulation monitoring device, and data from the vision sensor from one or more delivery containers 250; and continuously inputs the current values ​​of the first to fourth pumps, the voltage values ​​of the first to third switches, and data from the vision sensor from one or more drive devices 130. Since information inherent to various components of multiple input devices is continuously sent out, it is not easy to determine, for example, the number of cells, cell size, and cell type obtained from which cell sorter of which inspection device. Therefore, the interface software converts information constructed in the data format inherent to the input devices into information constructed in the data format inherent to the operating software. The data format inherent to the operating software is constructed using a data model with a tree or network data structure representing the hierarchical relationships of the components of each input device, and various data models are pre-stored in the memory of the control device 284. For ease of understanding, information inherent to the input devices, such as the first current value and the second current value of the inspection device 285, is converted into a structured data format inherent to the operating software, such as inspection device ID / third cell sorter / first current value / cell count / cell size. Through this conversion process, the operating software can instantly utilize data from multiple components of multiple input devices.

[0147] According to the aforementioned stem cell information management system 200, since the shortest path and shortest time schedule is determined by considering the production schedules of multiple sealed production devices 101 when accepting a manufacturing order, it is possible to shorten the production time and achieve high-level quality management. Since the somatic cell collection vials 102 and stem cell freezing vials 103 in the sealed containers are equipped with individual identification devices 106 that include at least one of the following in addition to the provider ID: order ID, delivery ID, acceptance ID, manufacturing location ID, production device ID, preservation device ID, and storage location ID, it is possible to prevent cross-contamination and ensure traceability in case of anomalies. Furthermore, by applying the site system, based on big data from multiple and multiple components from multiple and multiple input devices, it is possible to instantly determine anomaly warning outputs and schedule corrections during delivery, inspection, manufacturing, and storage, thereby achieving shortened production time, high-level quality management, and eliminating manpower shortages.

[0148] 3. Cell delivery equipment

[0149] Figure 39 and Figure 40 This is a perspective view of the somatic cell delivery container 301 and the stem cell delivery container 302 in the cell delivery device 300 according to this embodiment. Figure 39As shown, the somatic cell delivery container 301 is configured to hold one or more somatic cell collection vials 102, and the one or more somatic cell collection vials 102 are equipped with an individual identification device 106 containing at least a provider ID, a manufacturing device ID, etc. Figure 40 As shown, the stem cell delivery container 302 is configured to contain one or more stem cell freezing vials 103, each of which is equipped with an individual identification device 106 containing at least a provider ID, manufacturing device ID, and storage location ID. In other embodiments, the stem cell delivery container 302 may be... Figure 5 The storage device 120 is shown. In this embodiment, a system for producing iPS cells from blood cells has been described, but it is understood that it can also be applied to systems for producing iPS cells from cells from skin, systems for producing ES cells from embryonic cells, and the like.

[0150] like Figure 2 and Figure 14 As shown, the cell delivery device 300 further includes a reading device 107 configured to read the provider ID, manufacturing device ID, storage location ID, etc., contained in the individual identification device 106, and a delivery vehicle for delivering the somatic cell delivery container 301 to the closed manufacturing device 101 based on the read manufacturing device ID, or for delivering the stem cell delivery container 302 to the stem cell storage location based on the read storage location ID. The delivery vehicle includes at least one of automobiles, railways, aircraft, ships, and automated vehicles. According to the configuration of this cell delivery device 300, cross-contamination can be prevented even when stem cells are manufactured simultaneously and in parallel using one or more closed manufacturing devices 101.

[0151] like Figure 23 and Figure 24 As shown, the somatic cell delivery container 301 further includes a heat preservation tool for maintaining a constant temperature inside the delivery container. This heat preservation tool is a heating and cooling device 253 comprising a temperature estimation unit 259 that estimates the temperature of the somatic cells located inside the delivery container, and a heating and cooling unit 261 that automatically heats or cools the cells in conjunction with the temperature data output from the temperature estimation unit 259 to maintain a constant temperature. The heating and cooling device 253 stores an upper limit temperature and a lower limit temperature, and outputs an abnormal temperature warning when the temperature data from the temperature estimation unit 259 exceeds the upper limit temperature or falls below the lower limit temperature. In other embodiments, the stem cell delivery container 302 may include this heating and cooling configuration.

[0152] Figure 41 This is a block diagram of the stem cell delivery container 302 according to this embodiment. Figure 40 and Figure 41As shown, the stem cell delivery container 302 includes a heat preservation device for maintaining a certain temperature inside the delivery container. The heat preservation device includes: a cooling medium 303 for cooling or freezing the stem cells located inside the delivery container; a cooling medium remaining amount sensor 129 for detecting the remaining amount of the cooling medium; a pre-cooling storage tank 305 detachably connected to the delivery container and containing the pre-cooling medium; and a pre-cooling medium supply device 306 for supplying the pre-cooling medium based on the remaining amount of the cooling medium. The stem cell delivery container 302 further includes a memory 307 for storing various data, a CPU 308 for controlling the entire stem cell delivery container, and a communication control unit 309 capable of wirelessly communicating with a host computer. In other embodiments, the somatic cell delivery container 301 may include this pre-cooling medium supply configuration.

[0153] like Figure 41 As shown, the stem cell delivery container 302 further includes a pre-cooling medium remaining amount sensor 310 for detecting the remaining amount of the pre-cooling medium and a memory 307 for storing the upper and lower limits of the remaining amount of the pre-cooling medium. When the remaining amount of the pre-cooling medium is above the upper limit or below the lower limit, an abnormal warning of the remaining amount is output. In other embodiments, the somatic cell delivery container 301 can output this abnormal warning of the remaining amount.

[0154] like Figure 24 As shown, the somatic cell delivery container 301 and the stem cell delivery container 302 may further be equipped with a cumulative delivery time measuring device 254 for measuring the cumulative delivery time. The starting point for measuring the cumulative delivery time using the cumulative delivery time measuring device 254 is the date and time of somatic cell collection or the date and time of discharge from the stem cell frozen vial from the sealed preparation device. The cumulative delivery time measuring device 254 stores the time during which the somatic cells or stem cells can maintain their quality. When the cumulative delivery time exceeds the time during which the quality can be maintained, an abnormal time warning is output.

[0155] Figure 42 This is a flowchart illustrating the operation of the cell delivery device 300 according to this embodiment. When the temperature data from the temperature estimation unit (step S300), the remaining amount of the pre-prepared cold insulation medium (step S301), the cumulative delivery time (step S302), and the vibration value (step S303) are outside the normal range or within the abnormal range, the delivery containers 301 and 302 output at least one of the following abnormal warnings: temperature abnormality warning (step S304), remaining amount abnormality warning (step S305), time abnormality warning (step S306), and vibration abnormality warning (step S307), and transmit them wirelessly to a portable terminal 180 located at a remote distance.

[0156] Figure 43This is a functional block diagram of the site system applied in the cell delivery device 300 according to this embodiment. The cell delivery device 300 further includes a control device 320 having interface software 321 and operating software 322, and an input device connected to the control device 320 via wired or wireless connection for inputting information during the delivery process. Examples of input devices include the aforementioned somatic cell delivery container 301 and stem cell delivery container 302. In other embodiments, an input device for manually inputting information during the delivery process may be included.

[0157] The control device 320 continuously inputs data from one or more delivery containers 301, 302, such as the resistance value of a temperature sensor, temperature data from a temperature estimation unit, impedance of a somatic cell coagulation monitoring device, voltage value of a cold insulation medium remaining quantity sensor, voltage value of a pre-cold insulation medium remaining quantity sensor, and data from a vision sensor. Since information inherent to multiple components of the multiple input devices is constantly being sent out, it is not easy to determine, for example, the impedance of which vial in which delivery container. Therefore, the interface software converts information constructed in the data format inherent to the input devices into information constructed in the data format inherent to the operating software. The data format inherent to the operating software is constructed using a data model with a tree or network structure representing the hierarchical relationships of the components of each input device, and various data models are pre-stored in the memory of the control device 320. For ease of understanding, information inherent to the input devices, such as the impedance of the somatic cell coagulation monitoring device of the delivery container, is converted into a structured data format inherent to the operating software, such as delivery container ID / somatic cell coagulation monitoring device / 4th somatic cell collection vial / impedance / somatic cell coagulation value. Through this conversion process, the software can instantly utilize data from multiple input devices and multiple constituent elements.

[0158] With the aforementioned cell delivery device 300, since the somatic cell collection vial 102 contains the provider ID and the manufacturing device ID, or the stem cell freezing vial 103 contains the provider ID, the manufacturing device ID, and the storage location ID, it is possible to prevent cross-contamination and track abnormalities. Furthermore, by applying a site system, during delivery, based on the inherent information of multiple components in multiple delivery devices, abnormal warnings are instantly output and sent, thus enabling high-level quality management, reduced manufacturing time, and elimination of manpower shortages.

[0159] 4. Stem cell cryopreservation equipment

[0160] Figure 44 and Figure 45 This diagram illustrates the configuration of the stem cell cryopreservation apparatus 400 according to this embodiment. Figure 44As shown, the stem cell cryopreservation equipment 400 includes one or more cryopreservation devices 120 for cryopreserving stem cell vials 103, a storage container 401 for housing the cryopreservation devices 120, a conveying device 402 for moving the cryopreservation devices 120 into or out of the storage container 401, and a cold medium storage tank 404 connected to the one or more cryopreservation devices 120 via a cold medium supply line 403. The conveying device 402 is an automated device that operates according to a teaching procedure and connects the one or more cryopreservation devices 120 to the cold medium supply line 403.

[0161] like Figure 5 As described, the preservation device 120 includes: a receiving section 124 for accommodating one or more stem cell freezing vials 103; a freezing tank 125 for accommodating a cold-keeping medium for freezing the stem cell freezing vials 103; a cold-keeping medium remaining amount sensor 129 for detecting the remaining amount of the cold-keeping medium; a temperature sensor 128 for measuring the temperature of the receiving section 124; and a visual sensor 127 for detecting the presence of stem cells (or the presence of freezing solution) within the stem cell freezing vials 103. The individual identification device 106 for the stem cell freezing vials 103 within the preservation device 120 includes provider information including, in addition to provider ID, at least one of the following: informed consent form from the somatic cell provider, nationality, address, gender, age, blood type, past medical history, medication prescription history, health diagnosis results, and information on family members who have previously produced stem cells. Thus, in stem cell storage locations accommodating multiple preservation devices 120, it is easy to identify whose vial the stem cell freezing vial 103 is, and what characteristics it represents.

[0162] like Figure 5 As shown, the preservation device 120 further includes an in-situ sensor 121 for detecting the presence or absence of the stem cell cryopreservation vial 103. The stem cell cryopreservation equipment 400 further includes a conveying device (not shown) for moving the stem cell cryopreservation vial 103 into or out of the receiving portion 124 of the preservation device 120. The conveying device (not shown) moves the stem cell cryopreservation vial 103 into the receiving portion 124 of the preservation device 120 based on the detected presence or absence of the vial. The conveying device (not shown) is an automated device that operates automatically according to a teaching procedure.

[0163] like Figure 44 and Figure 45As shown, the stem cell cryopreservation device 400 further includes a control device 406 that monitors the operating status of the cryopreservation device 120 based on information from at least one of a residual volume sensor, a temperature sensor, and a vision sensor from one or more cryopreservation devices 120. The control device 406 stores the operating status of the cryopreservation device 120 as recorded information in a memory 407, associating it with time information and a provider ID. Additionally, the control device 406 stores at least one of the normal and abnormal operating status ranges in the memory 407. When the operating status falls outside the normal range or within the abnormal range, it outputs an abnormal warning, at least associated with the provider ID, and transmits it wired or wirelessly to a host computer 170 or a portable terminal 180 located at a remote location.

[0164] Figure 46 This is a functional block diagram of the site system used in the stem cell cryopreservation equipment 400 according to this embodiment. The control device 406 includes interface software 410, operating software 411, and an input device that is wired or wirelessly connected to the control device 406 for inputting information about the cryopreservation process. Examples of input devices include various cryopreservation devices 120, etc. In other embodiments, an input device for manually inputting information about the cryopreservation process may be included.

[0165] The control device 406 continuously inputs data from one or more storage devices 120, such as the resistance value of a temperature sensor, the voltage value of a remaining quantity sensor, data from a vision sensor, and the voltage value of a supply valve 412. Since information inherent to various components of multiple input devices is constantly being sent out, it is not easy to determine, for example, which component of which storage device 120 has a voltage value and what it indicates. Therefore, the interface software converts information in the data format inherent to the input devices into information in the data format inherent to the operating software. The data format inherent to the operating software is a data model with a tree or network structure representing the hierarchical relationships of the components of each input device, and various data models are pre-stored in the memory of the control device 406. For ease of understanding, information inherent to the input devices, such as data from the vision sensor of the storage device 120, is converted into a structured data format inherent to the operating software, such as storage device ID / vision sensor / data / presence / absence of stem cells (presence / absence of freezing fluid). Through this conversion process, the operating software can instantly utilize data inherent to various components of multiple input devices.

[0166] According to the aforementioned stem cell cryopreservation equipment 400, the operational status of the cryopreservation device 120 can be monitored at a stem cell storage location with long-term storage capabilities. Furthermore, the presence or absence of stem cells (or the presence or absence of freezing solution) within the cryopreservation device 120 can be managed. Moreover, by applying a site system, abnormal warnings can be instantly output and sent during storage based on information from multiple components within the multiple cryopreservation devices 120, thus achieving high-level quality management, reduced production time, and elimination of manpower shortages.

[0167] The software described in the foregoing embodiments can be provided by recording on a computer-readable non-volatile recording medium, such as a CD-ROM. It is understood that this specification has described various embodiments, but the present invention is not limited to the foregoing embodiments, and various modifications can be made within the scope of the following claims.

Claims

1. A stem cell information management system for centrally managing information in the following processes: accepting a manufacturing commission for stem cell production from somatic cells; transporting somatic cells collected from a somatic cell provider or stem cells produced from said somatic cells; inspecting said somatic cells or said stem cells; manufacturing process for producing said stem cells from said somatic cells; and storage process for storing said stem cells. The stem cell information management system has the following features: The storage department stores: the collection schedule for somatic cells from the somatic cell provider, the examination schedule for the somatic cells, the production schedule for one or more production devices for producing stem cells from the somatic cells, the storage schedule for one or more preservation devices for cryopreserving the produced stem cells, and the storage schedule for the location where the preservation devices are stored. The determination department, based on the stored collection schedule, inspection schedule, production schedule, storage schedule, and preservation schedule, determines at least the collection date for collecting the somatic cells from the somatic cell provider. A warning will be issued if the date resulting from adding the examination period and delivery period of the somatic cells to the examination schedule does not fall within the cell production period. The storage unit further stores the addresses of multiple somatic cell providers and the addresses of multiple collection agencies that collected the somatic cells. The determining unit further determines the collection agency, and determines the collection date based on the determined collection agency, which has the address closest to the address of one of the plurality of somatic cell providers.

2. The stem cell information management system according to claim 1, wherein the determining unit determines, based on the collection date of the somatic cells, the delivery date of the somatic cell collection kit to the somatic cell provider.

3. The stem cell information management system according to claim 2, wherein the somatic cell collection kit comprises a somatic cell collection vial for containing the collected somatic cells, and the somatic cell collection vial comprises a first somatic cell identification device comprising provider identification information for identifying the somatic cell provider and manufacturing device identification information for identifying the manufacturing device.

4. In the stem cell information management system according to claim 3, when accepting the commission for stem cell manufacturing, the storage unit associates and stores provider information containing at least one of the following: informed consent form of the somatic cell provider, nationality, address, gender, age, blood type, past medical records, prescription records of drugs, health diagnosis results, and information of family members who have previously produced stem cells, with the provider identification information.

5. The stem cell information management system according to claim 4, wherein the storage unit stores collection locations where the somatic cells can be collected, and the determining unit determines the collection date of the somatic cells based on the collection location closest to the address of the stored somatic cell provider and the collection schedule of the collection location.

6. The stem cell information management system according to claim 5, further comprising a delivery container configured to accommodate one or more of the somatic cell collection vials, the delivery container comprising at least one of the following: A heating and cooling device comprising a temperature estimation unit that estimates the temperature of the somatic cells within the delivery container, and a heating and cooling unit that automatically heats or cools the cells in a manner linked to temperature data from the temperature estimation unit to maintain the temperature at a constant level. A cumulative time measuring device that measures the cumulative conveying time of the conveying container. A coagulation monitoring device monitors the coagulation state of the somatic cells in the somatic cell collection vial. A vibration sensor that detects the vibration of the conveying container; The storage unit stores transport information including at least one of the temperature data, the cumulative transport time, a value obtained by quantifying the solidification state, and a value obtained by quantifying the vibration. The determining unit determines the output of abnormal warnings and schedule corrections during transportation based on the stored transportation information.

7. The stem cell information management system according to claim 6, further comprising a first inspection device for checking whether the collected somatic cells are easily recombined, the storage unit storing inspection information from the first inspection device, and the determination unit determining, based on the stored inspection information, the output of an abnormal warning and the correction of the schedule during the inspection.

8. The stem cell information management system according to claim 7, wherein the first inspection device comprises at least one of a somatic cell number measuring device for measuring the number of somatic cells and a gene expression level measuring device for measuring gene expression level.

9. The stem cell information management system according to claim 8, wherein the determining unit determines whether the somatic cells are easily recombinant based on at least one of the somatic cell provider's age, past medical history, family information of those who have previously produced stem cells, the number of somatic cells, the presence or absence of expression of a specific gene, and the expression level of a specific gene.

10. The stem cell information management system according to any one of claims 7 to 9, further comprising a visual sensor for acquiring data within the fabrication apparatus, the storage unit storing data from the visual sensor, the determination unit determining, based on the stored data from the visual sensor, fabrication information including at least one of the following: size or growth rate of stem cell clusters, proportion of stem cell cluster sizes, number of stem cells, shape of stem cells, hue or pH of culture reagent, and presence or absence of differentiated cells differentiated from the stem cells, and determining, based on the fabrication information, abnormal warning output and schedule correction during fabrication.

11. The stem cell information management system according to claim 10, further comprising a second inspection device for inspecting the genomic information of the somatic cells and the genomic information of the stem cells, wherein the storage unit stores inspection information from the second inspection device, and the determination unit determines, based on the stored inspection information, whether the genomic information of the somatic cells is the same as the genomic information of the stem cells, and determines to output an abnormal warning and schedule correction during the inspection.

12. The stem cell information management system according to claim 10, further comprising a third inspection device for inspecting the HLA type of the somatic cells and the HLA type of the stem cells, wherein the storage unit stores inspection information from the third inspection device, and the determination unit determines, based on the stored inspection information, whether the HLA type of the somatic cells is the same as the HLA type of the stem cells, and determines to output an abnormal warning and schedule correction during the inspection.

13. The stem cell information management system according to any one of claims 3 to 9, further comprising one or more conveying devices for conveying the somatic cell collection vial to the manufacturing device based on the manufacturing device identification information included in the first individual identification device, wherein the determining unit determines the conveyance of the somatic cell collection vial based on the stored manufacturing schedule of the manufacturing device.

14. The stem cell information management system according to claim 13, wherein the conveying device conveys at least one of the stem cell preparation materials and the culture reagent to the preparation device, the storage unit stores inventory information of the stem cell preparation materials and the culture reagent, and the determining unit determines the conveying of at least one of the stem cell preparation materials and the culture reagent based on the stored inventory information.

15. The stem cell information management system according to claim 13, further comprising a stem cell freezing vial containing the stem cells frozen after fabrication, wherein the determining unit determines the expected discharge date and time of the stem cell freezing vial from the fabrication device based on the stored fabrication schedule.

16. The stem cell information management system according to claim 15, wherein the determining unit determines a correction to the expected discharge date and time based on the monitoring results of the manufacturing device, and the conveying device conveys the stem cell frozen vial discharged from the manufacturing device to the storage device based on the corrected expected discharge date and time.

17. The stem cell information management system according to claim 15, wherein the stem cell freezing vial is equipped with a second somatic identification device comprising provider identification information for identifying the somatic cell provider, manufacturing device identification information for identifying the manufacturing device, and preservation device identification information for identifying the preservation device.

18. The stem cell information management system according to claim 17, further comprising a reading device for reading information contained in at least one of the first individual identification device and the second individual identification device.

19. The stem cell information management system according to claim 15, wherein the storage unit stores the storage date and time of storing the stem cell frozen vial in the storage device, and the determining unit determines the storage period of the stem cell frozen vial based on the stored storage date and time.

20. The stem cell information management system according to any one of claims 1 to 9, further comprising: A control device equipped with interface software and operating software, and An input device that is wired or wirelessly connected to the control device and inputs information from each process step; The interface software converts information in the data format inherent to the input device into information in the data format inherent to the working software.

21. The stem cell information management system according to claim 10, further comprising at least one of the collection location and collection date, the delivery information and abnormal warning, the inspection information and abnormal warning, and the production information and abnormal warning being transmitted wirelessly to a portable terminal located at a remote distance.

22. The stem cell information management system according to any one of claims 1 to 9, wherein the somatic cells are blood cells or fibroblasts.

23. The stem cell information management system according to any one of claims 1 to 9, wherein the stem cells are iPS cells.

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